Greetings,
At my recent MPN specialist appointment she gave me the results of an Allele burden sample I provided a year ago. She stated it was at 30%. This is my first time testing for this. She took another sample to see if there will be any change from last year's sample. She was surprised that it was not tested when initially diagnosed in 2018 in CT. Is this a common test to be taken when diagnosed and what does it mean if the percentage increases?
Thank you,
Marybeth
While many Hematologists now routinely test allele burden, not all do. Those who do tend to be MPN Specialists who are in agreement that Variant Allele Frequency (VAF) is a valid biomarker. It is important to note that VAF tends to correlate with symptom burden and disease status; however, this is not an absolute correlation. VAF tends to gradually increase over time as the JAK2 mutated hematopoietic stem cells (HSCs) have a clonal advantage over wild-type HSCs.
Some MPN Specialists and people with MPNs use VAF as a biomarker for disease status and treatment success. I agree as does my MPN care team. We check once per year. It has reduced from 38% to 10%. I think this is a good thing.
Hope that answers your question.
Thank you, Hunter. Yes, that does answer my question. I am curious if it changed in a year.
hunter5582 how long were you on the Besremi before your VAF dropped from 38% to 10%?
I was one Pegasys from May 2021 - February 2022. Switched to Besremi Feb 2022. Did the JAK2 VAF in December 2022 = 9%. JAK2 in December 2023 = 10%.
Important to note that from 2020 to 2021 VAF increased from 26% to 38%.
While VAF seems to have plateaued, I hope that over time the VAF will drop some more. time will tell.
Do you think it was the Pegasys or Besremi that caused the steep drop? Or a little of both, and maybe there is no way to know. Just curious if it's something you discussed with your dr. Thanks for the reply.
I think it was both. I have not experienced any difference between Pegasys or Besremi in efficacy or side effects. Theoretically, Besremi would be easier to tolerate at higher doses but I do not know that real life experiences will bear that out.
In 2018 allelic burden (variant allele frequency (VAF) was just starting to be a diagnostic check. The mutation was discovered only in 2005. In 2018 very few clinics considered it important and esp that it was possible to reduce by therapy. Even today many Drs don't care about it.
The evidence that VAF matters is approaching overwhelming as trials and reports have emerged over the past few years. There are many threads here on the subject with one right now discussing it in (too much) detail:
healthunlocked.com/mpnvoice...
My first hematologist stated it would increase with time, (2020) and this was the state of the art at the time. I showed him the then-new results of the Besremi interferon trial pointing to large reductions, see this plot that I post frequently. It was news to him.
We now know that both interferon and Jakafi can reduce this VAF. Since your Dr is well focused on VAF, it's likely Dr will discuss these options with you. If not you should ask. Of course not everyone sees this benefit.
30% is in a range often seen with PV. If you're on HU it's the gray line in this plot, so you may see reductions in the first year or two. But for most it is not durable and goes back up. With IFN or Jakafi it can decrease for a longer term.
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Way back in 2008, Danish MPN specialists had discovered and reported that the drug interferon alfa-2b was capable of sharply reducing the Jak2v617f allele burden (they called it the mutation frequency) to undectable or near undectable levels in a subset of PV patients (see reference below). They considered these patients as having attained "complete molecular remissions" and "minimal residual disease."
This depends on the country where you live. In Holland and Belgium hematologists do not follow up your allele burden because they claim that there are no consequences for treatment. It is still part of diagnoses, and in Holland it is reimbursed. In Germany many haematologists do follow up on the allele burden. I have always thougt that medicine is an exact science, but with 'cultural' differences?
It is more than culture per se. There are differences in how individual providers view the significance of VAF as well as differences in how healthcare systems pay for services. There are also differences in the level of provider's MPN knowledge and awareness of the emerging thinking on MPNs.
It is clear that VAF does have significance; however, not all agree on what the significance is. The ability to reduce VAF is new to the hematology field. For many decades, this was not possible with the older medications used. It will take time and data collection/analysis to clarify the role that VAF plays in MPN disease status.
My own belief is that there will be changes to the standard of care for MPNs, perhaps in the near future. Ideally, consideration of VAF as well as the role of other genetic factors (e.g., non-driver mutations) will become a part of the recommended protocols.
The science will only move forward if there is support for the science. This is an area where we can play a role in advocacy. Support for organizations like MPN Voice is a good place to start.
It's some respects the matter is rather simple: If an ET or PV patient is diagnosed early, while their Jak2 allele burden is still under about 25% and if their AB declines to 0 - 2% while on interferon and if that patient has no seriously deleterious secondary mutations, chances are high that patient will be able to maintain their state of "Minimal Residual Disease" for potentially a lifetime if they continue to take a small, infrequent "maintenance dose" of interferon.
Unfortunately, for various reasons the vast majority of ET and PV patients are not diagnosed early.
JAK2 Allele Burden On Pegasys
Jak2 Allele Burden reveal
JAK2 Allele Frequency/Burden
Pegasys not working to lower Allele burden
Good news re allele burden
